Cardiac disease has high comorbidity with diabetes. Up to 45% of individuals with bradycardia or tachycardia also suffer from diabetes. Diabetes is a life-long disease marked by high concentrations of glucose in the blood. The sugar called glucose enters the bloodstream when food is digested. Glucose is a source of fuel for the body. In response to the glucose in the bloodstream, an organ called the pancreas makes the hormone insulin. The role of insulin is to move glucose from the bloodstream into muscle, fat, and liver cells, where it can be used as fuel. Individuals with diabetes either do not produce insulin (Type I diabetes) or are resistant to insulin (Type II diabetes). Consequently, the concentration of glucose in the blood in a person with diabetes may vary by a large amount dependent upon what they have eaten and the person's metabolic requirements. Variation in blood-glucose concentration can cause adverse consequences for diabetics and individuals with cardiac disease.
Studies have suggested that hypoglycemia (abnormally low blood-glucose) may precipitate transient atrial fibrillation, arrhythmia and tachycardia. Collier et al., “Transient Atrial Fibrillation Precipitated By Hypoglycaemia: Two Case Reports,” Postgraduate Medical journal 63, 895-897 (1987); Shimada at al., “Arrhythmia During Insulin-Induced Hypoglycemia in a Diabetic Patient,” Arch. Intern. Med. 144, 1068-9 (1984). It has been suggested that hypoglycemia-induced arrhythmia is a possible cause of sudden death during the sleep. Tattersall et al., “Unexplained Deaths of Type 1 Diabetic Patients,” Diabetic Med. 8(1):49-58 (1991). Moreover some studies show that although implanted defibrillators can cause a significant reduction in mortality in high-risk cardiac disease patients they have less impact on the rate of sudden death in sleeping patients with cardiac disease—called “dead-in-bed” syndrome. It is suggested that such deaths are the result of untreated hypoglycemia and consequent arrhythmia. Moreover, when hypoglycemia is present, the resultant arrhythmia may be resistant to treatment by pacing. In one case study hypoglycemia triggered supraventricular tachycardia and an antitachycardia pacemaker was ineffective until the blood-glucose concentration was increased. Rokas et al., “Proarrhythmic Effects of Reactive Hypoglycemia,” Pace 15, 373-376 (1992).
Blood-glucose concentration control is essential to the prevention of hypoglycemia and its adverse cardiac consequences. Blood-glucose concentration monitoring is the first step in blood-glucose concentration control. Typically, a sample of blood must be drawn and then the blood-glucose concentration assayed using color changing strips or an electrical device. To ensure proper dosage of insulin, individuals with diabetes use lancets to draw blood for conventional glucose measurements. A disadvantage of current blood-glucose concentration testing is that the painful process of drawing blood limits the number of times an individual is willing to take measurements. Even where external blood-glucose concentration monitoring does not require blood samples, it is still a disadvantage that the process requires active user intervention. Patients may forget to measure their blood-glucose concentration regularly and are not able to monitor their own blood-glucose concentration while sleeping.
A method for external monitoring of blood-glucose concentration without drawing blood is disclosed in a publication by Cho et al., entitled “Noninvasive Measurement of Glucose by Metabolic Heat Conformation Method,” Clinical Chemistry 50:10 1894-1898 (2004), which is incorporated herein by reference. This publication utilizes a metabolic heat conformation method which depends upon measuring body surface temperature and conductive and radiative heat losses from the subject. These heat losses are tied through the circulatory system to glucose metabolism, which is the primary source of heat generation in the body. Using analysis of the surface temperature measurements and external peripheral measurements of blood flow, hematocrit and oxygen saturation, and standard blood-glucose concentration measurements, the authors developed relationships between the external measurements that predicted measured blood-glucose concentration. The MHC method utilizes precise measurements of external heat loss to estimate the rate of glucose metabolism and then correlates that to the blood-glucose concentration. However, while the method disclosed by Cho et al. has the advantage that it does not require blood to be drawn, it still requires active user intervention. See, also, U.S. Pat. No. 5,795,305 entitled “Process And Device For Non-Invasive Determination Of blood-glucose concentration In Parts Of The Human Body” to Cho et al.; and U.S. Pat. No. 5,924,996 titled “Process And Device For Detecting The Exchange Of Heat Between The Human Body And The Invented Device And Its Correlation To The blood-glucose concentration In Human Blood” to Cho at al, both of which are incorporated herein by reference. Moreover, the method disclosed by Cho, because it requires external measurements of the heat lost at the surface of the human body, cannot be utilized in an implantable device.
In view of the many disadvantages of conventional external blood-glucose concentration monitoring techniques, implantable blood-glucose concentration monitors have been investigated. Such monitors typically require sensors for mounting directly within the blood stream. Most implantable glucose sensors that have been proposed are amperometric enzymatic biosensors which use immobilized glucose oxidase, an enzyme that catalyzes the oxidation of glucose to gluconic acid with the production of hydrogen peroxide. However, such amperometric enzymatic biosensors tend to clog very quickly. Thus, despite the demand for such a sensor, no implantable blood-glucose concentration sensor has yet achieved widespread use.
In view of the disadvantages of the state of the art with respect to glucose monitoring, it would be desirable to have an implantable system that could measure blood-glucose concentration reliably and accurately without the disadvantages of amperometric enzymatic biosensors.